calc_css: Find the steady state concentration and the day it is...

In httk: High-Throughput Toxicokinetics

Find the steady state concentration and the day it is reached.

Description

This function finds the day a chemical comes within the specified range of the analytical steady state venous blood or plasma concentration(from calc_analytic_css) for the multiple compartment, three compartment, and one compartment models, the fraction of the true steady state value reached on that day, the maximum concentration, and the average concentration at the end of the simulation.

Usage

calc_css(
  chem.name = NULL,
  chem.cas = NULL,
  dtxsid = NULL,
  parameters = NULL,
  species = "Human",
  f = 0.01,
  daily.dose = 1,
  doses.per.day = 3,
  days = 21,
  output.units = "uM",
  suppress.messages = FALSE,
  tissue = NULL,
  model = "pbtk",
  default.to.human = FALSE,
  f.change = 1e-05,
  adjusted.Funbound.plasma = TRUE,
  regression = TRUE,
  well.stirred.correction = TRUE,
  restrictive.clearance = TRUE,
  dosing = NULL,
  ...
)

Arguments

chem.name	Either the chemical name, CAS number, or parameters must be specified.
chem.cas	Either the chemical name, CAS number, or parameters must be specified.
dtxsid	EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
parameters	Chemical parameters from parameterize_pbtk function, overrides chem.name and chem.cas.
species	Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
f	Fractional distance from the final steady state concentration that the average concentration must come within to be considered at steady state.
daily.dose	Total daily dose, mg/kg BW.
doses.per.day	Number of doses per day.
days	Initial number of days to run simulation that is multiplied on each iteration.
output.units	Units for returned concentrations, defaults to uM (specify units = "uM") but can also be mg/L.
suppress.messages	Whether or not to suppress messages.
tissue	Desired tissue concentration (default value is NULL, will depend on model – see steady.state.compartment in model.info file for further details.)
model	Model used in calculation, 'pbtk' for the multiple compartment model,'3compartment' for the three compartment model, and '1compartment' for the one compartment model.
default.to.human	Substitutes missing animal values with human values if true (hepatic intrinsic clearance or fraction of unbound plasma).
f.change	Fractional change of daily steady state concentration reached to stop calculating.
adjusted.Funbound.plasma	Uses adjusted Funbound.plasma when set to TRUE along with partition coefficients calculated with this value.
regression	Whether or not to use the regressions in calculating partition coefficients.
well.stirred.correction	Uses correction in calculation of hepatic clearance for well-stirred model if TRUE for model 1compartment elimination rate. This assumes clearance relative to amount unbound in whole blood instead of plasma, but converted to use with plasma concentration.
restrictive.clearance	Protein binding not taken into account (set to 1) in liver clearance if FALSE.
dosing	The dosing object for more complicated scenarios. Defaults to repeated daily.dose spread out over doses.per.day
...	Additional arguments passed to model solver (default of solve_pbtk).

Value

frac	Ratio of the mean concentration on the day steady state is reached (baed on doses.per.day) to the analytical Css (based on infusion dosing).
max	The maximum concentration of the simulation.
avg	The average concentration on the final day of the simulation.
the.day	The day the average concentration comes within 100 * p percent of the true steady state concentration.

Author(s)

Robert Pearce, John Wambaugh

See Also

calc_analytic_css

Examples

calc_css(chem.name='Bisphenol-A',doses.per.day=5,f=.001,output.units='mg/L')

parms <- parameterize_3comp(chem.name='Bisphenol-A')
parms$Funbound.plasma <- .07
calc_css(chem.name='Bisphenol-A',parameters=parms,model='3compartment')

out <- solve_pbtk(chem.name = "Bisphenol A",
  days = 50,                                   
  daily.dose=1,
  doses.per.day = 3)
plot.data <- as.data.frame(out)

css <- calc_analytic_css(chem.name = "Bisphenol A")
library("ggplot2")
c.vs.t <- ggplot(plot.data,aes(time, Cplasma)) + geom_line() +
geom_hline(yintercept = css) + ylab("Plasma Concentration (uM)") +
xlab("Day") + theme(axis.text = element_text(size = 16), axis.title =
element_text(size = 16), plot.title = element_text(size = 17)) +
ggtitle("Bisphenol A")

print(c.vs.t)

httk documentation built on March 7, 2023, 7:26 p.m.